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Repetitive transcranial of magnetic stimulation (rTMS), as a new electrophysiological technique, has been used in treating neurological and psychiatric diseases in clinical. In recent years, rTMS has also been employed to explore the treatment options for post stroke cognitive impairment (PSCI). Studies showed that rTMS was beneficial to recovery of post-stroke aphasia, improvement of memory dysfunction and alleviation of hemispatial neglect. Moreover, it is safe for patient within the recommended parameters of safety guidance. rTMS exerts therapeutic effects by interfering with the reconstruction of cortical network, improving the cerebral blood flow and metabolism, adjusting the ion balance by modulating cortical excitability. In addition, rTMS could enhance synaptic plasticity, inhibit the apoptosis, and regulate the transmission of a variety of neurotransmitters. It was reviewed that the basic principles of rTMS, the efficacy, safety and mechanism of rTMS in the treatment of PSCI, as well as the current problems and prospects in this paper.

Vesicular glutamate transporters (VGLUTs), which include VGLUT1, VGLUT2 and VGLUT3, are responsible for the uploading of L-glutamate into synaptic vesicles. The expression pattern of VGLUTs determines the level of synaptic vesicle filling (i.e., glutamate quantal size) and directly influences glutamate receptors and glutamatergic synaptic transmission; thus, VGLUTs may play a key role in learning and memory in the central nervous system. To determine whether VGLUTs contribute to the degeneration or acquisition of learning and memory, we used an animal model for the age-related impairment of learning and memory, senescence-accelerated mouse/prone 8 (SAMP8). KM mice were divided into groups based on their learning and memory performance in a shuttle-box test. The expression of VGLUTs and synaptophysin (Syp) mRNA and protein in the cerebral cortex and hippocampus were investigated with real-time fluorescence quantitative PCR and western blot, respectively. Our results demonstrate that, in the cerebral cortex, protein expression of VGLUT1, VGLUT2, VGLUT3 and Syp was decreased in SAMP8 with age and increased in KM mice, which displayed an enhanced capacity for learning and memory. The protein expression of VGLUT2 and Syp was decreased in the hippocampus of SAMP8 with aging. The expression level of VGLUT1 and VGLUT2 proteins were highest in KM mouse group with a 76-100% avoidance score in the shuttle-box test. These data demonstrate that protein expression of VGLUT1, VGLUT2 and Syp decreases age-dependently in SAMP8 and increases in a learning- and memory-dependent manner in KM mice. Correlation analysis indicated the protein expression of VGLUT1, VGLUT2 and Syp has a positive correlation with the capacity of learning and memory., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a progressive, neurodegenerative disease, which primarily affects the elderly. Clinical signs of AD are characterized by the neuron loss and cognitive impairment. At gene and protein levels, the senescence-accelerated mouse/prone 8 (SAMP8) is a suitable animal model to investigate the fundamental mechanisms of age-related learning and memory deficits. Huang-Lian-Jie-Du decoction (HL), a well-known traditional Chinese medicinal prescription, has been employed in the treatment of wide range of disease conditions. Modern pharmacological studies have showed that HL possesses many effects, which include amelioration of learning and memory function of CNS. This paper investigated the gene expression patterns of hippocampus and cerebral cortex of SAMP8, which were treated with HL employing the cDNA microarray and real time quantitative RT-PCR techniques. The results showed that HL has the significant modulating effects on age-related changes of the gene expressions in the hippocampus and cerebral cortex in SAMP8, which include genes that involved in signal transduction (Dusp12, Rps6ka1, Rab26, Penk1, Nope, Leng8, Syde1, Phb, Def8, Ihpk1, Tac2, Pik3c2a), protein metabolism (Ttc3, Amfr, Prr6, Ube2d2), cell growth and development (Ngrn, Anln, Dip3b, Acrbp), nucleic acid metabolism (Fhit, Itm2c, Cstf2t, Ddx3x, Ercc5, Pcgfr6), energy metabolism (Stub1, Uqcr, Nsf), immune response (C1qb), regulation of transcription (D1ertd161e, Gcn5l2, Ssu72), transporter (Slc17a7, mt-Co1), nervous system development (Trim3), neurogila cell differentiation (Tspan2) and 24 genes whose biological function and process were still unknown. It was suggested by the changes of the 62 genes with HL treatment that the ameliorating effect of HL on the cognitive impairments of SAMP8 might be achieved by multi-mechanism and multi-targets.

The senescence accelerated mouse prone 8 (SAMP8), an animal model of Alzheimer's disease, has amyloid-β deposition in the brain. This study showed that β-secretase activity increased age-dependently in cerebral cortex of SAMP8 and SAMP8's control, SAM resistant/1 (SAMR1), and was higher in the hippocampus of SAMP8 than that of age-matched SAMR1. Cathepsin D activity also increased age-dependently in the cerebral cortex of SAMP8. There was no significant difference between SAMP8 and SAMR1 with regards to activity of cathepsin B. β-secretase activity had a positive correlation with cathepsin D activity in the cerebral cortex of SAMR1 and SAMP8. There was a tendency toward decreased mRNA expression of BACE1, cathepsin D, and cathepsin B in the hippocampus of SAMR1 and SAMP8 with aging. mRNA expression of cathepsin B was elevated significantly in the cerebral cortex of SAMP8 at 2 and 6 months of age compared to that of age-matched SAMR1, and similarly so was cathepsin D at 2 months. This data showed there was no correlation between mRNA expression and activity of β-secretase, cathepsin D, and cathepsin B in the brain of SAMR1 and SAMP8 with age. These findings also indicate it was cathepsin D, not cathepsin B, that contributed to β-secretase activity and the increased amyloid-β production in the SAMP8 brain. In addition, it was necessary to take into account the target selectivity of BACE1 and cathepsin D, not necessary to detect the mRNA expression, when SAMP8 was used as an animal model to determine the effect of β-secretase inhibitor. [ABSTRACT FROM AUTHOR]